The objective of this proposal is to eucidate the mechanism by which certain potential myelotoxins cause bone marrow damage. We will use as the prototype bone marrow injury induced by chloramphenicol (CAP). Two types of bone marrow toxicity from CAP will be further investigated: 1. Reversible bone marrow suppression. Further studies here will include: 1. detailed investigation of the metabolic effects of CAP on bone marrow mitochondria. b. A study of CAP-marrow cell interaction using in vitro marrow culture techniques the mechanism of the protective effect of colony stimulating factor on CFU-C and the possible protection by other modulators of granulopoiesis from the CAP effect will be explored. 2. CAP-induced Aplastic Anemia. Two possible pathogenetic mechanisms will be considered and pursued. a. A biochemical predisposition - the role of the P-NO2 group of CAP will be explored. The possibililty that bone marrow aplasia results from irreversible binding of CAP to mitochondrial ribosomes will be tested. Comparative studies with marrow obtained from susceptible subjects will be carried out. b. Immune Mechanisms - The possible role of humoral and cellular immune mechanism in marrow injury from CAP will also be investigated.